Credit: NPG

Jonathan Himmelfarb and colleagues have developed a novel method to bioengineer functional kidney microvasculature from human kidney peritubular microvascular endothelial cells (HKMECs). They suggest that their 3D microphysiologic system could be used to investigate mechanisms of kidney disease and potential therapies.

The researchers isolated HKMECs from adult nephrectomy samples and from fetal kidneys using an enrichment protocol that involved depleting epithelial cells and expanding the endothelial cell population in media supplemented with high concentrations of VEGF before flow-cytometric sorting. The purified HKMECs expressed endothelial cell genes and surface markers and formed sheets with adherens junctions and closed fenestrae in 2D culture. Functional assays and microarray analysis of gene expression patterns indicated that HKMECs had a higher tubulogenic potential and a lower angiogenic potential than human umbilical vein endothelial cells.

To recreate the kidney microvasculature, the researchers seeded purified HKMECs in a network of microvessels formed in collagen gel and cultured them under flow conditions. The HKMECs formed a thin layer of fenestrated endothelium and deposited a basement membrane along the walls of the collagen microvessels. The resulting reconstituted kidney microvasculature formed a permeability barrier that prevented the transfer of solutes from the lumen into the matrix.

The researchers conclude that in their microphysiologic system, HKMECs exhibit properties that are highly representative of the kidney microvasculature in vivo. They are continuing to refine their approach to bioengineer the kidney microvasculature, as well as using their microphysiologic system to investigate mechanisms of toxic kidney injury.